01792nas a2200217   4500008004100000245010400041210007000145260001300215300001100228490000700239520104100246100001701287700002001304700002101324700002201345700001501367700002401382700001601406700002501422856012701447       2011                        eng d00aThe three-dimensional folding of the α-globin gene domain reveals formation of chromatin globules.0 athreedimensional folding of the αglobin gene domain reveals form  c2011 Jan  a107-140 v183 a<p>We developed a general approach that combines chromosome conformation capture carbon copy (5C) with the Integrated Modeling Platform (IMP) to generate high-resolution three-dimensional models of chromatin at the megabase scale. We applied this approach to the ENm008 domain on human chromosome 16, containing the &alpha;-globin locus, which is expressed in K562 cells and silenced in lymphoblastoid cells (GM12878). The models accurately reproduce the known looping interactions between the &alpha;-globin genes and their distal regulatory elements. Further, we find using our approach that the domain folds into a single globular conformation in GM12878 cells, whereas two globules are formed in K562 cells. The central cores of these globules are enriched for transcribed genes, whereas nontranscribed chromatin is more peripheral. We propose that globule formation represents a higher-order folding state related to clustering of transcribed genes around shared transcription machineries, as previously observed by microscopy.</p>1 aBaù, Davide1 aSanyal, Amartya1 aLajoie, Bryan, R1 aCapriotti, Emidio1 aByron, Meg1 aLawrence, Jeanne, B1 aDekker, Job1 aMarti-Renom, Marc, A  uhttp://clinbioinfosspa.es/content/three-dimensional-folding-%CE%B1-globin-gene-domain-reveals-formation-chromatin-globules